Relationship of LVEF and Myocardial Scar to Long-Term Mortality Risk and Mode of Death in Patients With Nonischemic Cardiomyopathy.

BACKGROUND: Nonischemic cardiomyopathy is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging is increasingly recognized as a risk marker for adverse outcomes; however, left ventricular dysfunction remains the basis for determining a patient's eligibility for primary prophylaxis with implantable cardioverter-defibrillator. We investigated the relationship of LVEF and scar with long-term mortality and mode of death in a large cohort of patients with nonischemic cardiomyopathy. METHODS: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with nonischemic cardiomyopathy who underwent clinical cardiovascular magnetic resonance imaging for the assessment of LVEF and scar at 3 centers. RESULTS: During a median follow-up of 5.2 (interquartile range, 3.8, 6.6) years, 277 (27%) patients died. On survival analysis, LVEF ≤35% and scar were strongly associated with all-cause (log-rank test P=0.002 and P<0.001, respectively) and cardiac death (P=0.001 and P<0.001, respectively). Whereas scar was strongly related to sudden cardiac death (SCD; P=0.001), there was no significant association between LVEF ≤35% and SCD risk (P=0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value but insignificant discrimination improvement by C-statistic for all-cause and cardiac death, but no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all 3 end points. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death (11.0%; 95% CI, -6.2% to 25.9%), cardiac death (9.8%; 95% CI, -5.7% to 29.3%), or SCD (7.5%; 95% CI, -41.2% to 42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI, 11.7% to 41.0%) for all-cause death, 27.0% (95% CI, 11.6% to 45.2%) for cardiac death, and 40.6% (95% CI, 10.5% to 71.8%) for SCD. CONCLUSIONS: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with nonischemic cardiomyopathy. However, whereas myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical measures. Scar assessment should be incorporated into patient selection criteria for primary prevention implantable cardioverter-defibrillator placement.

A Randomized Controlled Trial of Mobile Health Intervention in Patients With Heart Failure and Diabetes.

BACKGROUND: Mobile health (mHealth) platforms can affect health behaviors but have not been rigorously tested in randomized trials. OBJECTIVES: We sought to evaluate the effectiveness of a pragmatic mHealth intervention in patients with heart failure (HF) and diabetes (DM). METHODS: We conducted a multicenter randomized trial in 187 patients with both HF and DM to assess an mHealth intervention to improve physical activity and medication adherence compared to usual care. The primary endpoint was change in mean daily step count from baseline through 3 months. Other outcomes included medication adherence, health-related quality of life and metabolomic profiling. RESULTS: The mHealth group had an increase in daily step count of 151 steps/day at 3 months, whereas the usual-care group had a decline of 162 steps/day (least squares mean between-group difference = 313 steps/day; 95% CI: 8 619; P = 0.044). Medication adherence, measured using the Voils Adherence Questionnaire, did not change from baseline to 3 months (LS-mean change -0.08 in mHealth vs -0.15 in usual care; P = 0.47). The mHealth group had an improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score compared to the usual-care group (LS-mean difference = 5.5 points, 95% CI: 1.4, 9.6; P = 0.009). Thirteen metabolites, primarily medium- and long-chain acylcarnitines, changed differently between treatment groups from baseline to 3 months (P < 0.05). CONCLUSIONS: In patients with HF and DM, a 3-month mHealth intervention significantly improved daily physical activity, health-related quality of life and metabolomic markers of cardiovascular health but not medication adherence. CONDENSED ABSTRACT: Heart failure (HF) and diabetes (DM) have overlapping biological and behavioral risk factors. We conducted a multicenter randomized, clinical trial in 187 patients with both HF (regardless of ejection fraction) and DM to assess whether an mHealth intervention could improve physical activity and medication adherence. The mHealth group had an increase in mean daily step count and quality of life but not in medication adherence. Medium- and long-chain acylcarnitines changed differently in treatment groups from baseline to 3 months (P < 0.05). These data have important implications for designing effective lifestyle interventions in HF and DM.

PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure: Results of the PRIME-HF Trial.

BACKGROUND: Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS: PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated ß-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, ß-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS: Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, ß-blocker use/dose, and safety events were similar (all P > .05). CONCLUSIONS: Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing ß-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

Utilizing mobile technologies to improve physical activity and medication adherence in patients with heart failure and diabetes mellitus: Rationale and design of the TARGET-HF-DM Trial.

Heart failure (HF) and diabetes mellitus (DM) are major public health issues that place significant burden on patients and health care systems. Patients with both HF and DM are at higher risk of adverse cardiovascular and HF outcomes than those with either disease in isolation. Different antihyperglycemic medications (even within the same medication class) have conflicting results of benefit or harm in patients with established and incident HF. Recent data highlight the importance of a renewed focus on optimal pharmacotherapy for this population with DM and HF (or at risk for HF). Both HF and DM require major lifestyle modification for optimal management, in terms of both optimizing health behaviors (eg, physical activity, diet) and adherence to complex medical and self-care regimens. Mobile health (mHealth) technologies (eg, apps, wearables) are widely available in the community and may play a role in optimizing the health status of patients; however, there is limited and conflicting information on whether such technologies are actually beneficial in at-risk populations. In this article, we summarize current strategies, including mobile health interventions, to improve physical activity levels, drug adherence, and outcomes in patients with DM, HF, or both and describe the design and rationale for the Technologies to improve drug Adherence and Reinforce Guideline based Exercise Targets in patients with heart Failure and Diabetes Mellitus trial, which is designed to test the efficacy of using mHealth technology to improve health behaviors and outcomes in this high-risk population.

Association of left atrial volume index and all-cause mortality in patients referred for routine cardiovascular magnetic resonance: a multicenter study.

BACKGROUND: Routine cine cardiovascular magnetic resonance (CMR) allows for the measurement of left atrial (LA) volumes. Normal reference values for LA volumes have been published based on a group of European individuals without known cardiovascular disease (CVD) but not on one of similar United States (US) based volunteers. Furthermore, the association between grades of LA dilatation by CMR and outcomes has not been established. We aimed to assess the relationship between grades of LA dilatation measured on CMR based on US volunteers without known CVD and all-cause mortality in a large, multicenter cohort of patients referred for a clinically indicated CMR scan. METHOD: We identified 85 healthy US subjects to determine normal reference LA volumes using the biplane area-length method and indexed for body surface area (LAVi). Clinical CMR reports of patients with LA volume measures (n = 11,613) were obtained. Data analysis was performed on a cloud-based system for consecutive CMR exams performed at three geographically distinct US medical centers from August 2008 through August 2017. We identified 10,890 eligible cases. We categorized patients into 4 groups based on LAVi partitions derived from US normal reference values: Normal (21-52 ml/m2), Mild (52-62 ml/m2), Moderate (63-73 ml/m2) and Severe (> 73 ml/m2). Mortality data were ascertained for the patient group using electronic health records and social security death index. Cox proportional hazard risk models were used to derive hazard ratios for measuring association of LA enlargement and all-cause mortality. RESULTS: The distribution of LAVi from healthy subjects without known CVD was 36.3 ± 7.8 mL/m2. In clinical patients, enlarged LA was associated with older age, atrial fibrillation, hypertension, heart failure, inpatient status and biventricular dilatation. The median follow-up duration was 48.9 (IQR 32.1-71.2) months. On univariate analyses, mild [Hazard Ratio (HR) 1.35 (95% Confidence Interval [CI] 1.11 to 1.65], moderate [HR 1.51 (95% CI 1.22 to 1.88)] and severe LA enlargement [HR 2.14 (95% CI 1.81 to 2.53)] were significant predictors of death. After adjustment for significant covariates, moderate [HR 1.45 (95% CI 1.1 to 1.89)] and severe LA enlargement [HR 1.64 (95% CI 1.29 to 2.08)] remained independent predictors of death. CONCLUSION: LAVi determined on routine cine-CMR is independently associated with all-cause mortality in patients undergoing a clinically indicated CMR.

Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).

BACKGROUND: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. METHODS: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months. RESULTS: Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P<0.001). In CTA, 54.0% of events (n=74/137) occurred in patients with nonobstructive CAD (1%-69% stenosis). Prevalence of obstructive CAD and myocardial ischemia was low (11.9% versus 12.7%, respectively), with both findings having similar prognostic value (hazard ratio, 3.74; 95% confidence interval [CI], 2.60-5.39; and 3.47; 95% CI, 2.42-4.99). When test findings were stratified as mildly, moderately, or severely abnormal, hazard ratios for events in comparison with normal tests increased proportionally for CTA (2.94, 7.67, 10.13; all P<0.001) but not for corresponding functional testing categories (0.94 [P=0.87], 2.65 [P=0.001], 3.88 [P<0.001]). The discriminatory ability of CTA in predicting events was significantly better than functional testing (c-index, 0.72; 95% CI, 0.68-0.76 versus 0.64; 95% CI, 0.59-0.69; P=0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550.

Left Ventricular Long-Axis Function Assessed with Cardiac Cine MR Imaging Is an Independent Predictor of All-Cause Mortality in Patients with Reduced Ejection Fraction: A Multicenter Study.

Purpose To evaluate the prognostic value of a simple index of left ventricular (LV) long-axis function-lateral mitral annular plane systolic excursion (MAPSE)-in a large multicenter population of patients with reduced ejection fraction (EF) who were undergoing cardiac magnetic resonance (MR) imaging. Materials and Methods This retrospective study included 1040 consecutive patients (mean age, 59.5 years ± 15.8) at four U.S. medical centers who were undergoing cardiac MR imaging for assessment of LV dysfunction with EF less than 50%. Lateral MAPSE was measured in the four-chamber cine view. The primary end point was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between lateral MAPSE and death. The incremental prognostic value of lateral MAPSE was assessed in nested models. Results During a median follow-up of 4.4 years, 132 patients died. With Kaplan-Meier analysis, the risk of death increased significantly with decreasing tertiles of lateral MAPSE (log-rank P = .0001). Patients with relatively preserved lateral MAPSE (>9 mm) had very few deaths, regardless of whether their EF was above or below 35%. Patients with late gadolinium enhancement (LGE) and low lateral MAPSE had significantly reduced survival compared to those with LGE and high lateral MAPSE (log-rank P < .0001). Lateral MAPSE was independently associated with risk of death after adjustment for clinical and imaging risk factors, which were univariate predictors (age, body mass index, diabetes, LV end-diastolic volume index, LGE, EF) (hazard ratio = 2.051 per mm decrease; 95% confidence interval [CI]: 1.520, 2.768; P < .001). Inclusion of lateral MAPSE in this model resulted in significant improvement in model fit (likelihood ratio test P < .0001) and C statistic (increasing from 0.675 to 0.844; P < .0001). Continuous net reclassification improvement was 1.036 (95% CI: 0.878, 1.194). Conclusion Lateral MAPSE measured during routine cine cardiac MR imaging is a significant independent predictor of mortality in patients with LV dysfunction, incremental to common clinical and cardiac MR risk factors-including EF and LGE. © RSNA, 2017.

Spironolactone for heart failure with preserved ejection fraction.

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 µmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Regional variation in patients and outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial.

BACKGROUND: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). METHODS AND RESULTS: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. CONCLUSIONS: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Comparison of stress cardiovascular magnetic resonance imaging (CMR) with stress nuclear perfusion for the diagnosis of coronary artery disease.

OBJECTIVES: To assess the diagnostic performance of stress cardiac magnetic resonance (stress CMR) vs stress single-photon emission computed tomography (SPECT) in patients presenting to the emergency department (ED) with chest pain. BACKGROUND: SPECT imaging is the most utilized outpatient procedure in the United States. The diagnostic accuracy of SPECT can be limited by soft tissue attenuation and low spatial resolution. Stress CMR has much higher spatial resolution and without the susceptibility to soft tissue attenuation. METHODS: Eighty-seven patients without a history of CAD presenting to the ED with chest pain were prospectively enrolled. Patients underwent both stress CMR and stress SPECT imaging within 12 hours of presentation. Both the stress imaging tests were interpreted immediately for clinical purposes and coronary angiography was performed if either was abnormal. Patients were considered to have significant CAD if identified by angiography (≥50%) or if a cardiac event (cardiac death, myocardial infarction or revascularization) occurred during follow-up (mean 2.6 ± 1.1 years). RESULTS: Thirty-seven patients were referred for coronary angiography; 29 due to a positive stress test and eight patients for persistent chest pain despite two negative stress tests. There were 22 patients who had significant CAD (≥50%). The remaining patients were followed for 2.6 ± 1.1 years. At the conclusion of the follow-up period, there were four clinical events. The sensitivity, specificity, and diagnostic accuracy of CMR are 85%, 93%, and 89%, respectively. The sensitivity, specificity, and diagnostic accuracy of stress SPECT are 84%, 91%, and 88%, respectively. CONCLUSION: Stress CMR has similar diagnostic accuracy as stress SPECT in diagnosis of CAD.

Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial.

BACKGROUND: p38 MAPK inhibition has potential myocardial protective effects. We assessed losmapimod, a potent oral p38 MAPK inhibitor, in patients with non-ST-segment elevation myocardial infarction (NSTEMI) in a double-blind, randomised, placebo-controlled trial. METHODS: From October, 2009, to November, 2011, NSTEMI patients were assigned oral losmapimod (7·5 mg or 15·0 mg loading dose followed by 7·5 mg twice daily) or matching placebo in a 3:3:2 ratio. Safety outcomes were serious adverse events and alanine aminotransferase (ALT) concentrations over 12 weeks, and cardiac events (death, myocardial infarction, recurrent ischaemia, stroke, and heart failure) at 90 days. Efficacy outcomes were high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) concentrations at 72 h and 12 weeks, and troponin I area under the curve (AUC) over 72 h. The losmapimod groups were pooled for analysis. This trial is registered with ClinicalTrials.gov, number NCT00910962. FINDINGS: Of 535 patients enrolled, 526 (98%) received at least one dose of study treatment (losmapimod n=388 and placebo n=138). Safety outcomes did not differ between groups. HsCRP concentrations at 72 h were lower in the losmapimod group than in the placebo group (geometric mean 64·1 nmol/L, 95% CI 53·0-77·6 vs 110·8 nmol/L, 83·1-147·7; p=0·0009) but were similar at 12 weeks. Early geometric mean BNP concentrations were similar at 72 h but significantly lower in the losmapimod group at 12 weeks (37·2 ng/L, 95% CI 32·3-42·9 vs 49·4 ng/L, 38·7-63·0; p=0·04). Mean troponin I AUC values did not differ. INTERPRETATION: p38 MAPK inhibition with oral losmapimod was well tolerated in NSTEMI patients and might improve outcomes after acute coronary syndromes. FUNDING: GlaxoSmithKline.

Stress cardiac MR imaging compared with stress echocardiography in the early evaluation of patients who present to the emergency department with intermediate-risk chest pain.

PURPOSE: To compare the utility and efficacy of stress cardiac magnetic resonance (MR) imaging and stress echocardiography in an emergency setting in patients with acute chest pain (CP) and intermediate risk of coronary artery disease (CAD). MATERIALS AND METHODS: Written informed consent was obtained from all patients. This HIPAA-compliant study was approved by the institutional review board for research ethics. Sixty patients without history of CAD presented to the emergency department with intermediate-risk acute CP and were prospectively enrolled. Patients underwent both stress cardiac MR imaging and stress echocardiography in random order within 12 hours of presentation. Stress imaging results were interpreted clinically immediately (blinded interpretation was performed months later), and coronary angiography was performed if either result was abnormal. CAD was considered significant if it was identified at angiography (narrowing >50% ) or if a cardiac event (death or myocardial infarction) occurred during follow-up (mean, 14 months ± 5 [standard deviation]). McNemar test was used to compare the diagnostic accuracy of techniques. RESULTS: Stress cardiac MR imaging and stress echocardiography had similar specificity, accuracy, and positive and negative predictive values (92% vs 96%, 93% vs 88%, 67% vs 60%, and 100% vs 91%, respectively, for clinical interpretation; 90% vs 92%, 90% vs 88%, 58% vs 56%, and 98% vs 94%, respectively, for blinded interpretation). Stress cardiac MR imaging had higher sensitivity at clinical interpretation (100% vs 38%, P = .025), which did not reach significance at blinded interpretation (88% vs 63%, P = .31). However, multivariable logistic regression analysis showed stress cardiac MR imaging to be the strongest independent predictor of significant CAD (P = .002). CONCLUSION: In patients presenting to the emergency department with intermediate-risk CP, adenosine stress cardiac MR imaging performed within 12 hours of presentation is safe and potentially has improved performance characteristics compared with stress echocardiography. Online supplemental material is available for this article.

Utilization of trained volunteers decreases 30-day readmissions for heart failure.

Background: This study evaluated the effectiveness of using trained volunteer staff in reducing 30-day readmissions of congestive heart failure (CHF) patients.Methods: From June 2010 to December 2010, 137 patients (mean age 73 years) hospitalized for CHF were randomly assigned to either: an interventional arm (arm A) receiving dietary and pharmacologic education by a trained volunteer, follow-up telephone calls within 48 hours, and a month of weekly calls; ora control arm (arm B) receiving standard care. Primary outcomes were 30-day readmission rates for CHF and worsening New York Heart Association (NYHA) functional classification; composite and all-cause mortality were secondary outcomes.Results: Arm A patients had decreased 30-day readmissions (7% vs 19%; P ! .05) with a relative risk reduction (RRR) of 63% and an absolute risk reduction (ARR) of 12%. The composite outcome of 30-day readmission, worsening NYHA functional class, and death was decreased in the arm A (24% vs 49%;P ! .05; RRR 51%, ARR 25%). Standard-care treatment and hypertension, age $65 years and hypertension,and cigarette smoking were predictors of increased risk for readmissions, worsening NYHA functional class, and all-cause mortality, respectively, in the multivariable analysis.Conclusions: Utilizing trained volunteer staff to improve patient education and engagement might be an efficient and low-cost intervention to reduce CHF readmissions.

Routine cine-CMR for prosthesis-associated mitral regurgitation: a multicenter comparison to echocardiography.

BACKGROUND AND AIM OF THE STUDY: Mitral regurgitation (MR) is an important complication after prosthetic mitral valve (PMV) implantation. Transthoracic echocardiography is widely used to screen for native MR, but can be limited with PMV. Cine-cardiac magnetic resonance (CMR) holds the potential for the non-invasive assessment of regurgitant severity based on MR-induced inter-voxel dephasing. The study aim was to evaluate routine cine-CMR for the visual assessment of PMV-associated MR. METHODS: Routine cine-CMR was performed at nine sites. A uniform protocol was used to grade MR based on jet size in relation to the left atrium (mild < 1/3, moderate 1/3-2/3, severe > 2/3). MR was graded in each long-axis orientation, with overall severity based on cumulative grade. Cine-CMR was also scored for MR density and pulmonary vein systolic flow reversal (PVSFR). Visual interpretation was compared to quantitative analysis in a single-center (derivation) cohort, and to transesophageal echocardiography (TEE) in a multicenter (validation) cohort. RESULTS: The population comprised 85 PMV patients (59% mechanical valves, 41% bioprostheses). Among the derivation cohort (n = 25), quantitative indices paralleled visual scores, with stepwise increases in jet size and density in relation to visually graded MR severity (both p = 0.001). Patients with severe MR had an almost three-fold increase in quantitative jet area (p = 0.002), and a two-fold increase in density (p = 0.04) than did other patients. Among the multicenter cohort, cine-CMR and TEE (Δ =. 2 ± 3 days) demonstrated moderate agreement (κ = 0.44); 64% of discordances differed by ≤ 1 grade (Δ = 1.2 ± 0.5). Using a TEE reference, cine-CMR yielded excellent diagnostic performance for severe MR (sensitivity, negative predictive value = 100%). Patients with visually graded severe MR also had more frequent PVSFR (p < 0.001), denser jets (p < 0.001), and larger left atria (p = 0.01) on cine-CMR. CONCLUSION: Cine-CMR is useful for the assessment of PMV-associated MR, which manifests concordant quantitative and qualitative changes in size and density of inter-voxel dephasing. Visual MR assessment based on jet size provides an accurate non-invasive means of screening for TEE-evidenced severe MR.

Utilization of trained volunteers decreases 30-day readmissions for heart failure.

BACKGROUND: This study evaluated the effectiveness of using trained volunteer staff in reducing 30-day readmissions of congestive heart failure (CHF) patients. METHODS: From June 2010 to December 2010, 137 patients (mean age 73 years) hospitalized for CHF were randomly assigned to either: an interventional arm (arm A) receiving dietary and pharmacologic education by a trained volunteer, follow-up telephone calls within 48 hours, and a month of weekly calls; or a control arm (arm B) receiving standard care. Primary outcomes were 30-day readmission rates for CHF and worsening New York Heart Association (NYHA) functional classification; composite and all-cause mortality were secondary outcomes. RESULTS: Arm A patients had decreased 30-day readmissions (7% vs 19%; P < .05) with a relative risk reduction (RRR) of 63% and an absolute risk reduction (ARR) of 12%. The composite outcome of 30-day readmission, worsening NYHA functional class, and death was decreased in the arm A (24% vs 49%; P < .05; RRR 51%, ARR 25%). Standard-care treatment and hypertension, age ≥65 years and hypertension, and cigarette smoking were predictors of increased risk for readmissions, worsening NYHA functional class, and all-cause mortality, respectively, in the multivariable analysis. CONCLUSIONS: Utilizing trained volunteer staff to improve patient education and engagement might be an efficient and low-cost intervention to reduce CHF readmissions.

Recurrent coronary artery thrombosis after anomalous right coronary artery re-implantation to the aorta.

Anomalous origin of the right coronary artery (RCA) from the pulmonary artery is a rare entity. The current recommendation is corrective operation even in asymptomatic patients when this cardiac malformation is found. We report a case of a 21-year-old male who initially presented with ST elevations. After surgical repair with re-implantation of the RCA to the aorta, he was found to have an acute thrombus in his left circumflex and several months later developed a thrombus in the proximal left anterior descending artery. We propose that the change from a hyperkinetic high flow state to a slow flow state in the setting of inadequate coronary flow reserve and endothelial function predisposed our patient to thrombus formation in the persistently dilated coronary arteries. It is expected that restoration of normal flow pattern in all coronary arteries will result in normalization of perfusion, decrease in feeding artery size, and return of endothelial function. Because this anomaly is rare, limited information exists on the effects of the procedure on myocardial perfusion. These findings raise the question of whether re-implantation of the anomalous artery is truly the superior approach.

EPC mobilization after erythropoietin treatment in acute ST-elevation myocardial infarction: the REVEAL EPC substudy.

Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elevation myocardial infarction. In a substudy, we aimed to determine the feasibility of cryopreserving and centrally analyzing EPC levels to assess the relationship between EPC numbers, EPO administration, and infarct size. As a prespecified substudy, mononuclear cells were locally cryopreserved before as well as 24 and 48-72 h after primary percutaneous coronary intervention. EPC samples were collected in 163 of 222 enrolled patients. At least one sample was obtained from 125 patients, and all three time points were available in 83 patients. There were no significant differences in the absolute EPC numbers over time or between EPO- and placebo-treated patients; however, there was a trend toward a greater increase in EPC levels from 24 to 48-72 h postintervention in patients receiving ≥30,000 U of EPO (P = 0.099 for CD133(+) cells, 0.049 for CD34(+) cells, 0.099 for ALDH(br) cells). EPC numbers at baseline were inversely related to infarct size (P = 0.03 for CD133(+) cells, 0.006 for CD34(+) cells). Local whole cell cryopreservation and central EPC analysis in the context of a multicenter randomized trial is feasible but challenging. High-dose (≥30,000 U) EPO may mobilize EPCs at 48-72 h, and baseline EPC levels may be inversely associated with infarct size.

Quality of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation in the community setting.

BACKGROUND: The benefit of oral anticoagulation therapy with warfarin for stroke prevention in atrial fibrillation (AF) is directly dependent on the quality of anticoagulation (QoA), which in the US is provided predominantly in the community setting. With the emergence of new oral anticoagulation agents, the current QoA needs to be assessed. OBJECTIVES: The purpose of our study is to define the QoA with warfarin in patients with nonvalvular AF who are managed exclusively in community practices, and to compare the quality in the community setting with the quality demonstrated in the recent large randomized control trials. In addition, this study will assess the differences in the QoA based on cardiology vs primary care practices. METHODS: This is a retrospective, observational, multi-center study of 392 patients with AF in the community who were initiated on anticoagulation with warfarin for stroke prevention. International Normalized Ratio (INR) values were collected over a one-year period and the QoA was expressed as time in therapeutic range (TTR) calculated by the linear interpolation method. RESULTS: One hundred patients from cardiology practices and 292 patients from primary care were studied. During the one-year period, the overall mean TTR was 56.7%. The TTR in the primary care vs cardiology practices was 55.3% vs. 60.8% (p=0.02). Both practices had similar percent of time below therapeutic range, 29.8% vs. 29.2%. However, the primary care practice patients were above the therapeutic range 15% of the time vs. 10% in cardiology (p<0.001). There were one death secondary to intracranial bleed and one major bleed in the primary care group. There were no strokes during the study period in either group. CONCLUSION: The QoA with warfarin, as assessed by TTR, in the current community setting remains suboptimal, and there has been little to no improvement in current clinical practices. TTR should be considered when assessing the recent comparative studies evaluating novel pharmacologic agents to warfarin for the treatment of AF. SUBJECT AREAS: Arrhythmias, preventive cardiology, anticoagulation, thromboembolism, cardiovascular disease risk factors.

Sex-Specific Stress Perfusion Cardiac Magnetic Resonance Imaging in Suspected Ischemic Heart Disease: Insights From SPINS Retrospective Registry.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of mortality in women, but current noninvasive cardiac imaging techniques have sex-specific limitations. OBJECTIVES: In this study, the authors sought to investigate the effect of sex on the prognostic utility and downstream invasive revascularization and costs of stress perfusion cardiac magnetic resonance (CMR) for suspected CVD. METHODS: Sex-specific prognostic performance was evaluated in a 2,349-patient multicenter SPINS (Stress CMR Perfusion Imaging in the United States [SPINS] Study) Registry. The primary outcome measure was a composite of cardiovascular death and nonfatal myocardial infarction; secondary outcomes were hospitalization for unstable angina or heart failure, and late unplanned coronary artery bypass grafting. RESULTS: SPINS included 1,104 women (47% of cohort); women had higher prevalence of chest pain (62% vs 50%; P < 0.0001) but lower use of medical therapies. At the 5.4-year median follow-up, women with normal stress CMR had a low annualized rate of primary composite outcome similar to men (0.54%/y vs 0.75%/y, respectively; P = NS). In contrast, women with abnormal CMR were at higher risk for both primary (3.74%/y vs 0.54%/y; P < 0.0001) and secondary (9.8%/y vs 1.6%/y; P < 0.0001) outcomes compared with women with normal CMR. Abnormal stress CMR was an independent predictor for the primary (HR: 2.64 [95% CI: 1.20-5.90]; P = 0.02) and secondary (HR: 2.09 [95% CI: 1.43-3.08]; P < 0.0001) outcome measures. There was no effect modification for sex. Women had lower rates of invasive coronary angiography (3.6% vs 7.3%; P = 0.0001) and downstream costs ($114 vs $171; P = 0.001) at 90 days following CMR. There was no effect of sex on diagnostic image quality. CONCLUSIONS: Stress CMR demonstrated excellent prognostic performance with lower rates of invasive coronary angiography referral in women. Stress CMR should be considered as a first-line noninvasive imaging tool for the evaluation of women. (Stress CMR Perfusion Imaging in the United States [SPINS] Study [SPINS]; NCT03192891).

ACR Appropriateness Criteria® Pulsatile Abdominal Mass, Suspected Abdominal Aortic Aneurysm: 2023 Update.

Abdominal aortic aneurysm (AAA) is defined as abnormal dilation of the infrarenal abdominal aortic diameter to 3.0 cm or greater. The natural history of AAA consists of progressive expansion and potential rupture. Although most AAAs are clinically silent, a pulsatile abdominal mass identified on physical examination may indicate the presence of an AAA. When an AAA is suspected, an imaging study is essential to confirm the diagnosis. This document reviews the relative appropriateness of various imaging procedures for the initial evaluation of suspected AAA. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.